An Improved Assessment Method to Estimate (Poly)phenol Intake in Adults with Chronic Pancreatitis.

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

Simultaneous enhancement of multiple functional properties using evolution-informed protein design.

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.g., EVcouplings), which leverage extensive information about various protein properties and activities from homologous protein sequences, have proven effective for many applications including structure determination and mutation effect prediction. We apply EVcouplings to computationally design variants of the model protein TEM-1 ß-lactamase. Nearly all the 14 experimentally characterized designs were functional, including one with 84 mutations from the nearest natural homolog. The designs also had large increases in thermostability, increased activity on multiple substrates, and nearly identical structure to the wild type enzyme. This study highlights the efficacy of evolutionary models in guiding large sequence alterations to generate functional diversity for protein design applications.

Relationships between Habitual Polyphenol Consumption and Gut Microbiota in the INCLD Health Cohort.

While polyphenol consumption is often associated with an increased abundance of beneficial microbes and decreased opportunistic pathogens, these relationships are not completely described for polyphenols consumed via habitual diet, including culinary herb and spice consumption. This analysis of the International Cohort on Lifestyle Determinants of Health (INCLD Health) cohort uses a dietary questionnaire and 16s microbiome data to examine relationships between habitual polyphenol consumption and gut microbiota in healthy adults (n = 96). In this exploratory analysis, microbial taxa, but not diversity measures, differed by levels of dietary polyphenol consumption. Taxa identified as exploratory biomarkers of daily polyphenol consumption (mg/day) included Lactobacillus, Bacteroides, Enterococcus, Eubacterium ventriosum group, Ruminococcus torques group, and Sutterella. Taxa identified as exploratory biomarkers of the frequency of polyphenol-weighted herb and spice use included Lachnospiraceae UCG-001, Lachnospiraceae UCG-004, Methanobrevibacter, Lachnoclostridium, and Lachnotalea. Several of the differentiating taxa carry out activities important for human health, although out of these taxa, those with previously described pro-inflammatory qualities in certain contexts displayed inverse relationships with polyphenol consumption. Our results suggest that higher quantities of habitual polyphenol consumption may support an intestinal environment where opportunistic and pro-inflammatory bacteria are represented in a lower relative abundance compared to those with less potentially virulent qualities.

Fat malabsorption in pancreatic cancer: Pathophysiology and management.

Exocrine pancreatic insufficiency (EPI) is common in pancreatic ductal adenocarcinoma (PDAC) and may lead to significant nutrition compromise. In the setting of cancer cachexia and gastrointestinal toxicities of cancer treatments, untreated (or undertreated) EPI exacerbates weight loss, sarcopenia, micronutrient deficiencies, and malnutrition. Together, these complications contribute to poor tolerance of oncologic therapies and negatively impact survival. Treatment of EPI in PDAC involves the addition of pancreatic enzyme replacement therapy, with titration to improve gastrointestinal symptoms. Medical nutrition therapies may also be applicable and may include fat-soluble vitamin replacement, medium-chain triglycerides, and, in some cases, enteral nutrition. Optimizing nutrition status is an important adjunct treatment approach to improve quality of life and may also improve overall survival.

Interventions for Pancreatitis-New Approaches, Knowledge Gaps, and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.

Fat-soluble vitamin deficiency and exocrine pancreatic insufficiency among adults with chronic pancreatitis: Is routine monitoring necessary for all patients?

Chronic pancreatitis (CP) is often associated with exocrine pancreatic insufficiency (EPI), which may increase risk for fat-soluble vitamin depletion. Although vitamin D deficiency is widespread among the general population, vitamins A, E, and K deficiencies may more uniquely present in patients with CP. Yet, it is unclear whether fat-soluble vitamin status should be routinely monitored in all patients with CP or limited to those with EPI. The purpose of this review is to describe the laboratory status of vitamins A, E, and K in adult patients with CP and their association with exocrine pancreatic function. Five primary, observational studies met the inclusion criteria for qualitative synthesis. Biochemical deficiencies in fat-soluble vitamins were observed across trials but results varied with respect to whether EPI increased risk. Challenges related to the diagnosis and treatment of EPI along with potential confounders may contribute to the heterogeneity among study results. Although more studies are needed to determine the influence of pancreatic enzyme replacement therapy on fat-soluble vitamin status as well as effective vitamin repletion strategies, clinicians should consider periodically screening for deficiencies in all patients with CP regardless of EPI to avoid associated health effects of vitamin depletion.

Multicenter evaluation of the Selux Next-Generation Phenotyping antimicrobial susceptibility testing system.

The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials. Data is provided for all organism-antimicrobial combinations evaluated, including those that did and did not meet FDA performance requirements. Overall very major error and major error rates were less than 1% (31/3,805 and 107/15,606, respectively), essential agreement and categorical agreement were >95%, reproducibility was ≥95%, and the average time-to-result (from time of assay start to time of MIC result) was 5.65 hours.

Celiac Disease: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline.

Celiac disease is an autoimmune disorder in which the immune system of genetically susceptible individuals elicits a reaction to gluten causing small intestine damage. If left undiagnosed and untreated, the resulting nutrition malabsorption can lead to anemia, bone disease, growth faltering, or other consequences. The condition is lifelong and lacks a cure; the only treatment is lifelong adherence to a gluten-free diet (GFD). This diet is challenging to follow and adversely influences quality of life; however, it is essential to ensure intestinal recovery and prevent future negative health consequences. The Academy of Nutrition and Dietetics convened an expert panel complemented by a celiac disease patient advocate to evaluate evidence for six topics, including medical nutrition therapy; the GFD; oat consumption; micronutrients; pro-/prebiotics; and the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. This publication outlines the Academy of Nutrition and Dietetics Evidence Analysis Library methods used to complete the systematic review and guideline development, and summarizes the recommendations and supporting evidence. The guidelines affirm that all individuals with celiac disease should follow a GFD (1C, Imperative) that may include gluten-free oats in adults (2D, Conditional). Children should follow a nutritionally adequate GFD that supports healthy growth and development (Consensus, Imperative) and does not unnecessarily restrict gluten-free oats (Consensus, Conditional). The guidelines indicate nutritional care should include routine nutritional assessment (Consensus, Imperative) and medical nutrition therapy (Consensus, Imperative). At this time, the guidelines do not support a recommendation for the addition of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (2C, Conditional); prebiotic or probiotic supplementation (2D, Conditional); or micronutrient supplementation (in the absence of nutritional deficiency) (Consensus, Conditional). The 2021 Celiac Disease Evidence-Based Nutrition Guideline will assist registered dietitian nutritionists in providing appropriate evidence-based medical nutrition therapy to support people with celiac disease in achieving and maintaining nutritional health and avoiding adverse celiac disease consequences throughout their lives.

Comparison of predictive equations and indirect calorimetry in critical care: Does the accuracy differ by body mass index classification?

BACKGROUND: Nutrition support professionals are tasked with estimating energy requirements for critically ill patients. Estimating energy leads to suboptimal feeding practices and adverse outcomes. Indirect calorimetry (IC) is the gold standard for determining energy expenditure. However, access is limited, so clinicians must rely on predictive equations. METHODS: A retrospective chart review of critically ill patients who underwent IC in 2019 was conducted. The Mifflin-St Jeor equation (MSJ), Penn State University equation (PSU), and weight-based nomograms were calculated using admission weights. Demographic, anthropometric, and IC data were extracted from the medical record. Data were stratified by body mass index (BMI) classifications, and relationships between estimated energy requirements and IC were compared. RESULTS: Participants (N = 326) were included. Median age was 59.2 years, and BMI was 30.1. The MSJ and PSU were positively correlated with IC in all BMI classes (all P < 0.001). Median measured energy expenditure was 2004 kcal/day, which was 1.1-fold greater than PSU, 1.2-fold greater than MSJ, and 1.3-fold greater than weight-based nomograms (all P < 0.001). CONCLUSION: Despite the significant relationships between measured and estimated energy requirements, the significant fold-differences suggest that using predictive equations leads to significant underfeeding, which may result in poor clinical outcomes. Clinicians should rely on IC when available, and increased training in the interpretation of IC is warranted. In the absence of IC, the use of admission weight in weight-based nomograms could serve as a surrogate, as these calculations provided the closest estimate to IC in participants with normal weight and overweight, but not obesity.

Simultaneous enhancement of multiple functional properties using evolution-informed protein design.

Designing optimized proteins is important for a range of practical applications. Protein design is a rapidly developing field that would benefit from approaches that enable many changes in the amino acid primary sequence, rather than a small number of mutations, while maintaining structure and enhancing function. Homologous protein sequences contain extensive information about various protein properties and activities that have emerged over billions of years of evolution. Evolutionary models of sequence co-variation, derived from a set of homologous sequences, have proven effective in a range of applications including structure determination and mutation effect prediction. In this work we apply one of these models (EVcouplings) to computationally design highly divergent variants of the model protein TEM-1 ß-lactamase, and characterize these designs experimentally using multiple biochemical and biophysical assays. Nearly all designed variants were functional, including one with 84 mutations from the nearest natural homolog. Surprisingly, all functional designs had large increases in thermostability and most had a broadening of available substrates. These property enhancements occurred while maintaining a nearly identical structure to the wild type enzyme. Collectively, this work demonstrates that evolutionary models of sequence co-variation (1) are able to capture complex epistatic interactions that successfully guide large sequence departures from natural contexts, and (2) can be applied to generate functional diversity useful for many applications in protein design.

Navigating nutrition and hydration care in the adult patient with short bowel syndrome.

Attending diligently to the nutrition and hydration needs of patients with short bowel syndrome (SBS) is a key tenet of their care, both postoperatively and in the years that follow. For, without each, patients are left to themselves to navigate the nutrition consequences of SBS, including malnutrition, nutrient deficiencies, renal compromise, osteoporosis, fatigue, depression, and impaired quality of life. The intent of this review is to discuss the initial nutrition assessment, oral diet, hydration, and home nutrition support for the patient with SBS.

The evaluation and management of macronutrient deficiency dermatoses.

In industrialized countries, nutritional dermatoses are likely underdiagnosed and result in increased disease morbidity and utilization of hospital resources. These findings underscore the need for physicians to be able to correctly identify these deficiencies. Nutritional dermatoses may be split into micronutrient deficiencies and macronutrient deficiencies. This article is intended to serve as a supplement to a 2-part review of micronutrient deficiency dermatoses and highlights cutaneous findings in patients with protein-energy malnutrition and essential fatty acid deficiency. This article reviews the evaluation, cutaneous manifestations, and management of macronutrient deficiencies.

Identification of Malnutrition Risk Using Malnutrition Screening Tool in an Ambulatory Pancreas Clinic.

OBJECTIVES: The aim of this project was to assess malnutrition risk in a well-defined cohort of pancreatic diseases. METHODS: We performed a retrospective, cross-sectional study of 401 subjects with available malnutrition screening tool scores who received care at a single outpatient pancreas clinic during a 6-month study period. Univariate analyses were performed to compare demographic, anthropometric, symptoms/diseases, and risk for malnutrition characteristics across 3 strata of diseases: acute pancreatitis (n = 141), chronic pancreatitis (n = 193), and other pancreatic diagnoses (n = 67). RESULTS: A total of 18% of subjects were identified as at risk for malnutrition, including 25% who reported involuntary weight loss and/or decreased appetite. Subjects categorized as at risk for malnutrition were more likely to have gastrointestinal symptoms. Although the nutrition consultation rates were higher in subjects at risk for malnutrition (P = 0.03), 66% did not receive a clearly indicated dietary evaluation or management recommendations. One fifth of all patients in an ambulatory pancreas clinic are identified as at risk for malnutrition using a simple, validated tool. CONCLUSIONS: The majority of patients at increased risk for nutritional complications did not receive nutritional recommendations.

The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses. Part 2: B-complex vitamins.

Nutritional dermatoses are traditionally taught in the context of developing countries, famine, population displacement, and limited access to health care. In the United States, nutritional dermatoses may be underdiagnosed, leading to increased morbidity and utilization of hospital resources. These findings underscore the need for providers in developed nations to be able to identify these deficiencies. Dermatologists play a critical role in the diagnosis and management of patients with nutritional deficiencies, as they often present with cutaneous findings. Part 2 of this review series will focus on the epidemiology, impact, manifestations, and diagnosis of B-complex vitamins, which can present with cutaneous findings, including thiamine, riboflavin, niacin, pyridoxine, and biotin.

Risk factors and assessment considerations for essential fatty acid deficiency in nonparenterally fed patients using a case example.

Essential fatty acid deficiency (EFAD) has most commonly been reported in parenterally fed individuals but may also present in patients receiving fat-restricted diets and in patients with fat-malabsorption disorders. This article reviews the physical and biochemical assessment for EFAD in clinical practice and disorders of fat malabsorption as potential risk factors for EFAD. A case report is included to describe the fatty acid profile of a patient with exocrine pancreatic insufficiency receiving low-dose pancreatic enzyme replacement therapy after a self-imposed fat-restricted diet. The current challenges with laboratory interpretation of essential fatty acid status are also discussed.

The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses part 1: Zinc, selenium, copper, vitamin A, and vitamin C.

Dermatologists play a critical role in diagnosing and managing nutritional deficiencies as they often present with cutaneous findings. Traditionally, nutritional dermatoses are taught in the context of developing countries, famine, population displacement, and poor health care access; however, in the United States, common risk factors include chronic liver disease, alcoholism, psychiatric disease, bariatric surgery, inflammatory bowel disease, and hemodialysis. Additionally, nutritional dermatoses may be underdiagnosed in the United States and result in increased morbidity and utilization of hospital resources. There is a need for providers in developed nations to identify these deficiencies, and this review aims to meet that practice gap and provide relevant context to these diseases for dermatologists. This 2-part review series will focus on the epidemiology, impact, appearance, and diagnostic modalities for micronutrient deficiencies, including zinc, selenium, copper, and vitamins A and C in part 1. The companion review will focus on the B-complex vitamins.

Stevens-Johnson syndrome associated with Hodgkin's lymphoma.

Hodgkin's lymphoma accounts for approximately 40% of all lymphomas presenting in childhood and can be associated with a variety of dermatologic manifestations. Here, we describe a case of Hodgkin's lymphoma presenting with Stevens-Johnson syndrome. Clinicians should be aware of this association, especially if no alterative trigger for Stevens-Johnson syndrome can be identified.

The prevalence of aberrations in body composition in pediatric cystic fibrosis patients and relationships with pulmonary function, bone mineral density, and hospitalizations.

BACKGROUND: Body mass index (BMI) correlates with clinical outcomes in cystic fibrosis but has limitations.  Body composition aberrations in CF are multifactorial. We sought to evaluate body composition and relationships with pulmonary function, bone health, and hospital admissions. Other aims included defining body composition indices in a cohort of children with CF. METHODS: We conducted a retrospective review of patients with CF, age 8-18 years, seen at Nationwide Children's Hospital (2015-2020). Indices of body composition measured by dual-energy x-ray absorptiometry(DXA) scans.  Data included fat mass, fat-free mass (FFM), forced expiratory volume in one second (FEV1%), bone mineral density (BMD), and hospital admissions. NWA was defined as BMI 5th-85th percentile, body fat percentage >85th percentile. FFMD defined as FFMI <10th percentile. STATISTICS: T-tests compared NWA, FFMD and clinical measurements. Pearson correlations analyzed fat-free mass index (FFMI), fat mass index (FMI), BMI and clinical measurements. RESULTS: This study included 114 patients.  Mean age 12 years, 72 female. A high prevalence of FFMD existed (n=66, 38.6%).  FMI and FFMI correlated with FEV1% (r: 0.23, p:0.01, r: 0.36, p<0.001, respectively) and BMD (r: 0.29, p:0.002). FMI and hospital admissions were related (r:-0.23,p:0.01). FFMD was associated with 9.5% lower FEV1% (p=0.001) and lower BMD Z-score by 1.1 (p<0.001) when compared to no FFMD. CONCLUSION: This cohort of children with CF had a high prevalence of FFMD and low prevalence of NWA.  FFMD was associated with worsened clinical measurements. Patients with FFMD need additional exercise or nutritional intervention. Heterogeneity of body composition definitions creates need for more research.